Allergy最新文献

{"title":"Type-2-Inflammatory-Diseases Share Comorbidities, Molecular Signatures, IL4/IL13 Genetics, and Response to IL4/IL13 Blockade.","authors":"Jennifer D Hamilton, Manuel A R Ferreira, Wei Keat Lim, Carlo Sidore, Matthew F Wipperman, Wenzhen Ge, Xue Song, Changming Xia, Julie E Horowitz, Andrea T Hooper, Sara C Hamon, Jennifer Maloney, Jamie M Orengo, Zhen Chen, Stephanie Amato Ricci, Bolanle Akinlade, Aris Baras, Gary Herman, Brandy L Bennett, George D Yancopoulos","doi":"10.1111/all.70380","DOIUrl":"10.1111/all.70380","url":null,"abstract":"<p><strong>Background: </strong>It has long been appreciated that multiple allergic/atopic conditions (type-2-inflammation-associated diseases, T2IDs) often appear in the same individual, suggesting a shared systemic immune deviation. Emerging molecular and clinical investigations of interleukin (IL)4/IL13 blockade with the fully-human antibody dupilumab suggest that many are driven by over-activation of the IL4/IL13 pathway, manifesting differently in distinct tissues.</p><p><strong>Methods and results: </strong>We performed comprehensive quantitative analyses using several large, independent datasets (including real-world and clinical trial datasets) to confirm that many T2IDs-including asthma, atopic dermatitis, eosinophilic esophagitis, nasal polyps, prurigo nodularis-are highly interrelated based on co-prevalence, genetic predispositions, and transcriptomic signatures driven by over-activation of the IL4/IL13 pathway. We also summarize extensive clinical trial data showing that these T2IDs also share uniformly impressive clinical responses to dual IL4/IL13 blockade with dupilumab.</p><p><strong>Conclusions: </strong>While highly consistent with previous data and observations, this is the first systematic comparison of these types of data across multiple T2IDs, using a rigorous quantitative assessment of the largest datasets evaluated to date. Many T2IDs are not only highly interrelated and comorbid, but share transcriptomic signatures and genetic predispositions that suggest they all share over-activation of the IL4/IL13 pathway as a key causative driver, consistent with and explaining their uniform clinical responsiveness to dual IL4/IL13 blockade. These genetic and transcriptomic signatures may also have utility for identifying other diseases mediated by IL4/IL13 or T2-mediated subpopulations of heterogenous inflammatory diseases.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":"3345-3360"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13569704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired Clearance of Neutrophil Extracellular Traps in Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis","authors":"Manao Kinoshita, Youichi Ogawa, Natsumi Hama, Inkin Ujiie, Akito Hasegawa, Yasuyuki Fujita, Saeko Nakajima, Hayato Takahashi, Yoshiko Mizukawa, Shinji Shimada, Riichiro Abe, Tatsuyoshi Kawamura","doi":"10.1111/all.70507","DOIUrl":"https://doi.org/10.1111/all.70507","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"7 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silica Aggravates Steroid Hyporesponsiveness via STING Activation in House Dust Mite Lung Inflammation.","authors":"Bushra Mdkhana, Narjes Saheb Sharif-Askari, Mariam Wed Eladham, Shirin Hafezi, Baraa Khalid Salah Al-Sheakly, Sarra B Shakartalla, Hala Halwani, Fatemeh Saheb Sharif-Askari, Ibrahim Yaseen Hachim, Qutayba Hamid, Rabih Halwani","doi":"10.1111/all.70350","DOIUrl":"10.1111/all.70350","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":"3372-3376"},"PeriodicalIF":11.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13569655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Failed Mucosal Allostasis Distinguishes Murine IgG ‐ From IgE ‐Mediated Recurrent Severe Anaphylaxis","authors":"Abdurrahman Simsek, Muhammed Ali Kizmaz, Tugce Bozkurt, Sude Toprakkaz, Mehmet Emre Topcu, Musa Ozgur Ozyigit, Ahmet Akkoc, Dane Ediger, Ferah Budak Sener","doi":"10.1111/all.70503","DOIUrl":"https://doi.org/10.1111/all.70503","url":null,"abstract":"Background Anaphylaxis is classically framed around IgE‐FcεRI, yet a subset of severe reactions engages an IgG–FcγR‐mediated arm whose consequences for mucosal barrier integrity and epithelial repair remain undefined under recurrence. We propose that mucosal surfaces sustain function during severe anaphylaxis through coordinated operation of immunological composition, structural integrity and reparative capacity—which we term mucosal allostasis—and asked whether the two pathways diverge along this framework. Methods BALB/c mice were resolved into IgE‐ and IgG‐mediated arms using a hybrid active/passive (ASA‐PSA) sensitisation model and subjected to acute or recurrent severe anaphylaxis, with pharmacological reversal enabling matched rechallenge. Lung, small intestine, colon and serum were profiled across cytokine, mediator, junctional, repair and bacterial 16S rDNA panels; ILC subsets and junctional integrity were resolved by flow cytometry and immunohistochemistry. Results Despite comparable systemic clinical severity, the two pathways diverged sharply at the mucosal level. IgE‐mediated recurrence preserved junctional expression and mounted a coordinated AREG/EGF/periostin/TFF3/MUC2 repair programme, whereas IgG‐mediated recurrence dismantled both: Claudin‐1, Occludin, ZO‐1 and E‐cadherin declined in tissue and rose reciprocally in serum, repair mediators failed to engage where junctional injury was greatest, and bacterial DNA translocation rose 48‐fold, alongside a type 2/regulatory to inflammatory shift and an ILC2 to ILC1/NCR <jats:sup>+</jats:sup> ILC3 reorganisation. Conclusion Recurrent IgE‐ and IgG‐mediated severe anaphylaxis diverge into two mechanistically opposite allostatic phenotypes. IgG‐mediated recurrence produces an allostatic collapse in which structural failure proceeds uncoupled from reparative engagement, identifying barrier–repair coupling as a candidate axis for intervention in refractory anaphylaxis.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"22 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T Cell‐Intrinsic NEIL2 Restrains Th2 Allergic Inflammation by Regulating Chromatin Accessibility","authors":"Koa Hosoki, Aakash Sur, Annamalai Govindhan, Nisha Tapryal, Anirban Chakraborty, Maki Wakamiya, Robert L. Jacobs, Tapas K. Hazra, Sanjiv Sur","doi":"10.1111/all.70500","DOIUrl":"https://doi.org/10.1111/all.70500","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"21 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148858822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Need to Assess On-Demand Versus Continuous Treatment in Allergic Rhinitis in ARIA-EAACI Guidelines.","authors":"Jean Bousquet, Bernardo Sousa-Pinto, Maria J Torres, Mario Morais-Almeida, Ludger Klimek, Giorgio Ciprandi, Robert Naclerio, Torsten Zuberbier","doi":"10.1111/all.70498","DOIUrl":"https://doi.org/10.1111/all.70498","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human IgE Antibodies Recognize the Vicilin and Alpha-Hairpinin Domains of Peanut Allergen Ara h 1.","authors":"Taylor M Cosey, Gage O Leighton, Emmanuel R De Diavoukana, Min Shi, Alexander C Y Foo, Anna Pomés, Jacqueline B Nesbit, Stephen A Y Gipson, Paige Creeks, Jian Zhang, R Stokes Peebles, Soheila J Maleki, Derek Croote, Scott A Smith, Geoffrey A Mueller","doi":"10.1111/all.70495","DOIUrl":"https://doi.org/10.1111/all.70495","url":null,"abstract":"<p><strong>Background: </strong>Most peanut allergic patients have antibodies to Ara h 1. Many studies have focused on the C-terminal vicilin region, with less attention concentrated on the N-terminal α-hairpinin domain. This study evaluated human monoclonal antibodies targeted to both regions.</p><p><strong>Methods: </strong>Microarrays of Ara h 1 peptides were probed for serum IgE binding. Human monoclonal antibodies to Ara h 1 were discovered from single-cell sequencing and hybridoma technologies. Western blots evaluated the cleavage pattern of Ara h 1 in peanuts. A mouse model of passive systemic anaphylaxis (PSA) evaluated the functional coupling of antibodies. ELISAs established antibody specificities.</p><p><strong>Results: </strong>In 75 allergic patients, the most frequently recognized peptides from Ara h 1 were in the unstructured region (91%), the α-hairpinin (86%), and the vicilin region (79%). Monoclonal antibodies were divided by specificity for the α-hairpinin and vicilin regions with no significant cross-reactivity observed. The anti-α-hairpinin mAb 40C7 blocked 55%-92% of patient IgE to the domain in seven patients; ELISA results showed the epitope of 40C7 was associated with a frequently recognized peptide found via microarray. Pairing of anti-α-hairpinin mAbs failed to induce anaphylaxis via PSA; however, a single mAb against the vicilin region induced anaphylaxis when challenged with nAra h 1.</p><p><strong>Conclusions: </strong>The α-hairpinin of Ara h 1 contains a dominant epitope that is both frequently recognized and blocks a majority of the IgE against this domain. Including this region in tests may improve diagnosis of peanut allergy. The trimeric structure of the vicilin region explains the ability of Ara h 1 to induce anaphylaxis with a single antibody.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting Platelet-Activating Factor in Asthma: An Exploratory Metabolomics Analysis of PAF C-18:1 and Type 2 Inflammation.","authors":"Noeul Kang, Young Jin Pyung, Deog Kyeom Kim, Cheol-Heui Yun, Hyun Woo Lee","doi":"10.1111/all.70499","DOIUrl":"https://doi.org/10.1111/all.70499","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mepolizumab Modifies Blood Eosinophil Proteome and Transcriptome in Severe Eosinophilic Asthma.","authors":"Pablo Miguéns-Suárez, Sara Vázquez-Mera, Laura Martelo-Vidal, Marina Blanco Aparicio, Uxío Calvo Álvarez, Coral González Fernández, Mar Mosteiro Añón, Dolores Corbacho Abelaira, Tamara Hermida Valverde, Christian Calvo Henríquez, Susana B Bravo, Lena Uller, Juan J Nieto-Fontarigo, Francisco J Salgado, Francisco J González-Barcala","doi":"10.1111/all.70491","DOIUrl":"https://doi.org/10.1111/all.70491","url":null,"abstract":"<p><strong>Background: </strong>Mepolizumab, an anti-IL5 monoclonal antibody, effectively reduces exacerbations and improves disease control in severe eosinophilic asthma (SEA). While this treatment rapidly decreases blood eosinophil counts, some patients continue to experience asthma symptoms, suggesting that other features beyond eosinophil number contribute to disease persistence. In this work, we aim to characterize the molecular and functional signature of circulating eosinophils in SEA in response to mepolizumab therapy.</p><p><strong>Methods: </strong>We performed proteomic (LC-MS/MS) and targeted transcriptomic (Nanostring) analyses on isolated blood eosinophils from healthy individuals and SEA patients at baseline and after 4, 16 and 32 weeks of treatment with mepolizumab. Western blot was used to validate selected genes and proteins.</p><p><strong>Results: </strong>Eosinophils from healthy donors and post-treatment SEA patients exhibit lower levels of proteins related to cytoskeleton (e.g., GSN, DBNL, ARPC2 and ARPC3), suggesting a lower potential for migration and tissue extravasation. Several proteins (e.g., EPX and NCF2) and genes (e.g., CCL23 and SOCS3) directly involved in eosinophil effector functions, including ROS generation and degranulation, were significantly downregulated after mepolizumab treatment. The downregulation of GSN (actin-binding protein), NCF2 (subunit of the NADPH oxidase complex) and EPX (eosinophil-specific granule protein), was further validated by western blot.</p><p><strong>Conclusions: </strong>Our multi-omic analysis suggests that mepolizumab reduces the migratory capacity and effector-related molecular signatures of circulating eosinophils in SEA patients. Selected proteins, including GSN, NCF2 and EPX, may serve as candidate biomarkers for monitoring response to therapy.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":11.3,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Initial OX40 – OX40L Signaling Promotes a Skin‐Resident Memory T‐Cell Reservoir in Atopic Dermatitis","authors":"Takayoshi Komatsu‐Fujii, Ryota Asahina, Tatsuya Hasegawa, Satoshi Nakamizo, Saeko Nakajima, Toshiaki Kogame, Kenji Kabashima","doi":"10.1111/all.70493","DOIUrl":"https://doi.org/10.1111/all.70493","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"381 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}